Ex Parte Bruchez et alDownload PDFBoard of Patent Appeals and InterferencesMar 18, 200810631573 (B.P.A.I. Mar. 18, 2008) Copy Citation UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE BOARD OF PATENT APPEALS AND INTERFERENCES ____________ Ex parte MARCEL P. BRUCHEZ, HUGH R. DANIELS, STEPHEN A. EMPEDOCLES, VINCE E. PHILLIPS, EDITH Y. WONG and DONALD A. ZEHNDER ____________ Appeal 2008-1673 Application10/631,573 Technology Center 1600 ____________ Decided: March 19, 2008 ____________ Before TONI R. SCHEINER, DONALD E. ADAMS, and DEMETRA J. MILLS, Administrative Patent Judges. ADAMS, Administrative Patent Judge. DECISION ON APPEAL This appeal under 35 U.S.C. § 134 involves claims 1 and 46-53, the only claims pending in this application. We have jurisdiction under 35 U.S.C. § 6(b). Appeal 2008-1673 Application 10/631,573 INTRODUCTION The claims are directed to a method of spectral karyotyping a metaphase preparation of chromosomes. Claim 1 is illustrative: 1. A method of spectral karyotyping a metaphase preparation of chromosomes, comprising the steps of: (a) providing a metaphase preparation of chromosomes on a solid support, wherein the preparation comprises more than one chromosome; (b) combining said preparation with a plurality of semiconductor nanocrystal conjugates, each of said conjugates being specific for a nucleic acid molecule contained within each of said chromosomes, wherein each semiconductor nanocrystal conjugate has an emission spectrum distinct from the other semiconductor nanocrystal conjugates, wherein said combining is performed under conditions that allow formation of complexes comprising said conjugates and said nucleic acid molecule, when present; (c) removing any unbound conjugate; (d) detecting the presence of the complexes by monitoring a spectral emission mediated by the semiconductor nanocrystal in the complex, to provide a spectral karyotype. The Examiner relies on the following prior art references to show unpatentability: Bruchez US 6,274,323 B1 Aug. 14, 2001 Thomas Ried et al., Simultaneous visualization of seven different DNA probes by in situ hybridization using combinatorial fluorescence and digital imaging microscopy,” 89 Proc. Natl. Acad. Sci. USA 1388-92 (1992). E. Schröck et al., Multicolor Spectral Karyotyping of Human Chromosomes, 273 Science 494-97 (1996). 2 Appeal 2008-1673 Application 10/631,573 Marcel Bruchez Jr., et al., Semiconductor Nanocrystals as Fluorescent Biological Labels, 281 Science 2013-16 (1998). The rejection as presented by the Examiner is as follows: Claims 1 and 46-53 stand rejected under 35 U.S.C. § 103(a) as being unpatentable over the combination of Schröck, Ried and Bruchez. We affirm. DISCUSSION The claims have not been argued separately and therefore stand or fall together. 37 C.F.R. § 41.37(c)(1)(vii). Therefore, we limit our discussion to representative claims 1. Claim 1 is directed to a method of spectral karyotyping a metaphase preparation of chromosomes. The claimed method comprises four steps: (a) providing a metaphase preparation of chromosomes, comprising more than one chromosome, on a solid support; (b) combining the chromosome preparation of step (a) with a plurality of semiconductor nanocrystal conjugates; (c) removing any unbound conjugate; and (d) detecting the presence of the complexes by monitoring a spectral emission mediated by the semiconductor nanocrystal in the complex, to provide a spectral karyotype. Step (b) of claim 1 places limitations on each semiconductor nanocrystal conjugate. Specifically, each semiconductor nanocrystal conjugate of step (b): a. is specific for a nucleic acid molecule contained within each of said chromosomes; and 3 Appeal 2008-1673 Application 10/631,573 b. has an emission spectrum distinct from the other semiconductor nanocrystal conjugates. In addition, step (b) of claim 1 requires that the chromosome preparation of step (a) is combined with a plurality of semiconductor nanocrystal conjugates under conditions that allow formation of complexes comprising the semiconductor nanocrystal conjugates and the nucleic acid molecule contained within each of the chromosomes, when present. Appellants do not dispute and therefore concede to the Examiner’s finding that Schröck teaches every limitation of the claimed invention with the exception of the use of a solid support and semiconductor nanocrystals (Ans. 3-4). With regard to the use of a solid support, the Examiner finds that Schröck follows “the methodology of Reid . . . [which teaches the] preparation of chromosomes on slides (Ans. 3). Appellants do not dispute and therefore concede to the Examiner’s combination of Schröck and Reid. With regard to the use of semiconductor nanocrystals, the Examiner finds that Bruchez “teach[es] semiconductor nanocrystals which are used as fluorescent labels” (Ans. 5). In addition, the Examiner finds that Bruchez teaches that “[m]any sizes of nanocrystals may . . . be excited with a single wavelength of light, resulting in many emission colors that may be detected simultaneously” (id.). Further, the Examiner finds that Bruchez teaches that “[o]ver repeated scans, the nanocrystal-labeled samples showed very little photobleaching, far less than with conventional dye molecules” (Ans. 6). Based on this evidence, the Examiner finds that “[i]t would have been prima facie obvious to one of ordinary skill in the art at the time of the 4 Appeal 2008-1673 Application 10/631,573 invention to have used the semiconductor nanocrystals of Bruchez et al. as fluorescent labels in the spectral karyotyping method of Schrock” (Ans. 5). In response, Appellants assert that “[t]he use of semiconductor nanocrystals provides distinct advantages not contemplated in the prior art” (App. Br. 71). Specifically, Appellants assert that a very large number of chromosomal regions can be labeled simultaneously and “[t]he robustness of semiconductor nanocrystals alleviates the problem of contamination associated with degradation products encountered by organic dyes” (id.). According to Appellants, “Schrock does not address the need for fluorescent dyes with a wide range of tunable spectra” (id.). We note, however, that “[i]n determining whether the subject matter of a patent claim is obvious, neither the particular motivation nor the avowed purpose of the patentee controls. What matters is the objective reach of the claim. If the claim extends to what is obvious, it is invalid under § 103.” KSR Int’l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741-42 (2007); see also In re Beattie, 974 F.2d 1309, 1312 (Fed. Cir. 1992) (“[T]he law does not require that the references be combined for the reasons contemplated by the inventor.”). Accordingly, we are not persuaded by Appellants’ argument. Appellants assert that “[t]he Examiner alleges that a skilled artisan, faced with no knowledge of the present invention, would be motivated based on Schrock and Bruchez, to use unique, spectrally disparate dyes so that they could avoid Schrock’s detection methods for deconvolution of emission signals” (App. Br. 8). According to Appellants, “Schrock is directed to a 1 The Appeal Brief (App. Br.) is not paginated. Accordingly, we refer to page numbers as if the App. Br. were numbered consecutively beginning with the first page. 5 Appeal 2008-1673 Application 10/631,573 detection method for deconvolution of emission signals. The Examiner’s suggestion requires a substantial reconstruction and redesign of the elements shown in the primary reference as well as a change in the basic principle under which the primary reference construction was designed to operate” (App. Br. 9). In addition, Appellants assert that “at the time of filing, semiconductor nanocrystals were a new and fairly unconventional dye . . . . it is unlikely that one would be motivated, based on Bruchez, to use a new and fairly unconventional dye (at the time of filing), for the purpose of avoiding emission overlap, despite Schrock’s insistence upon the use of conventional dyes with overlapping emission spectra” (id.). We disagree. As the Examiner explains, Schröck provides a method in which combinations of five different fluorophores were used to label 24 probes, which were then used to stain metaphase chromosomes . . . . The method relies on using a custom-built filter set and software which provides Fourier transform-based spectral deconvolution . . . . Further, even though dyes with spectral overlap can be used, the overlap cannot be smaller than 15 nm . . . . In summary, this method presents a significant investment of time and resources. Therefore, one of ordinary skill in the art would look for a simpler solution. Such a solution is presented by Bruchez. (Ans. 6-7.) In this regard, the Examiner finds that Bruchez teaches “Semiconductor nanocrystals were prepared for use as fluorescent probes in biological staining and diagnostics. Compared with conventional fluorophores, the nanocrystals have a narrow, tunable, symmetric emission spectrum and are photochemically stable. The advantages of the broad, continuous excitation spectrum were demonstrated in a dual- emission, single-excitation labeling experiment on mouse fibroblasts. These nanocrystal probes are thus complementary and in some cases may be superior to existing fluorophores.” 6 Appeal 2008-1673 Application 10/631,573 (Ans. 7.) As the Examiner points out, Bruchez refers to Schröck’s teaching that combinatorial labeling has been used to generate 24 falsely colored probes for spectral karyotyping (2). Conventional dye molecules impose stringent requirements on the optical system used to make these measurements; their narrow excitation spectrum makes simultaneous excitation difficult in most cases, and their broad emission spectrum with a long tail at red wavelengths . . . introduces spectral cross talk between different detection channels, making quantitation of the relative amounts of different probes difficult. Ideal probes for multicolor experiments should emit at spectrally resolvable energies and have a narrow, symmetric emission spectrum, and the whole group of probes should be excitable at a single wavelength (3, 4). (Id.) From this the Examiner reasons one of ordinary skill in the art . . . would be motivated to accept the solution to cumbersome and complicated spectral labeling of Schrock et al. by replacing the fluorescent labels with semiconductor nanocrystals, as using the semiconductor nanocrystals would allow him/her to use already existing equipment. Ample motivation to do this is provided in Bruchez. (Ans. 8.) We find no error in the Examiner’s analysis. “When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability.” KSR, 127 S. Ct. 1727 at 1396. We disagree with Appellants’ intimation that a person of ordinary skill in this art would not have had a reasonable expectation of success simply because semiconductor 7 Appeal 2008-1673 Application 10/631,573 nanocrystal technology was “a new and fairly unconventional dye” as of Appellants’ filing date (App. Br. 9). Further, for the reasons provided by the Examiner (Ans. 8-9), we disagree with Appellants’ assertion that the modification of Schröck with the teachings of Bruchez would require a substantial reconstruction and redesign of Schröck (App. Br. 9). As the Examiner explains “the same basic principles of fluorescence detection apply in both cases: excite the fluorophore, measure emitted light. Thus, no change of principle of the operation applies here, only simplification of the excitation and detection processes from the method of Schrock” (Ans. 9). We also disagree with Appellants' statement that the combination of references relied upon by the Examiner “teach away from each other” (App. Br. 10). A reference is said to “teach away” from a claimed invention when it “suggests that the line of development flowing from the reference’s disclosure is unlikely to be productive of the result sought by the applicant” In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994). For the reasons set forth by the Examiner (Ans. 6-9) the preponderance of evidence on this record fails to support Appellants’ position. On reflection, we find that the preponderance of evidence on this record supports the Examiner’s conclusion that claim 1 is prima facie obvious in view of the combination of Schröck, Ried and Bruchez. Accordingly, we affirm the rejection of claim 1 under 35 U.S.C. § 103(a) as being unpatentable over the combination of Schröck, Ried and Bruchez. Claims 46-53 fall together with claim 1. 8 Appeal 2008-1673 Application 10/631,573 CONCLUSION In summary, we affirm the rejection of record. No time period for taking any subsequent action in connection with this appeal may be extended under 37 CFR § 1.136(a). AFFIRMED INVITROGEN CORPORATION C/O INTELLEVATE P.O. BOX 52050 MINNEAPOLIS MN 55402 lp 9 Copy with citationCopy as parenthetical citation